Fatigue overview and Definition

Disease overview:

Fatigue is a term used to represent the tiredness. It might be due to physical as well as mental health conditions .It often goes away with the rest. If it gets prolonged then the individual should get medical help. The fatigue can be classified as Acute and Chronic based on the duration of the symptoms occurrence


  1. Structural damage of white matter (WM) and grey matter (GM),
  2. Inflammatory processes (within or outside the central nervous system, CNS),
  3. Maladaptive network recruitment due to distributed lesions or inflammation,
  4. Metacognition (self-monitoring) of interoception of dyshomeostatic state.


Structural brain damage:

The white matter and the grey matter results in the mechanism of the fatigue.

White matter lesions:

Active dependent conduction block might contribute to fatigability. Fampridine is thought to improve the conduction of the action potentials in demyelinated nerves by blocking voltage gated potassium channels.

GM lesions:

Two different degenerative mechanisms in cortex, that is, inflammation-induced oxidative injury of neurons and retrograde neurodegeneration due to axonal transection. In subcortical regions, frequent sites of GM lesions include the thalamus, basal ganglia, amygdala, substantia nigra and hypothalamus.

Orexin a neuropeptide of basic importance of arousal and vigilance , in a patient with the narcolepsy a disease which dramatically reduces the vigilance and autoimmunological reactions against orexin producing neurons strongly decreases orexin levels. Lees production of orexin might results in fatigueness of individuals.transmitetr suppl

Lesions of dopaminergic, serotonergic or noradrenergic nuclei in the brainstem and the consequent reduction of monoaminergic transmitter supply to cortex and basal ganglia could explain the reduction in motivation. Grey matter lesions in hypothalamus or brainstem nuclei could disturb the hypothalamus pituitary adrenal axis  and descending neural control of the autonomic nervous system leading to persistent endocrine and autonomic disturbances.


Immunological and Inflammatory processes:

Peripheral immunological and inflammatory processes are likely to play a central role for fatigue.

Peripheral immunological and inflammatory processes are likely to play a central role for fatigue, in general, and in the specific context of MS. This is illustrated by ‘sickness behaviour’, a syndrome of fatigue, social withdrawal and lowered mood during common infections that trigger the production of proinflammatory cytokines. Furthermore, fatigue can be induced by immunomodulatory drugs like interferon-α or vaccinations that trigger production of proinflammatory cytokines.

Maladaptive network recruitment during task performance:

Regulate neuronal gain and excitability via slow afterhyperpolarisation currents mediated by calcium-dependent potassium channels second, they alter both short-term and long-term synaptic plasticity by modulating NMDA receptors. Rapid functional reorganisation of cortical networks in response to manipulations of neuromodulatory transmitters was demonstrated in human and animal studies, and it is conceivable that similar effects could arise from brainstem lesions in MS or through effects of inflammation on monoamine synthesis.

Metacognitive perspective on fatigue:

Dyshomeostatic state including immunological, metabolic, endocrine, cardiovascular, hepatic and renal diseases.

The diminished sensory attenuation during the execution of movements lead to proprioceptive prediction errors, requiring the brain to conclude that movements require more effort than predicted.

Clinical signs & symptoms

The person is lethargic in doing and beginning the activity

Postpone the activities

Not able to concentrate on simple things

The person gets easily tired once the activity is begun.


  1. If the fatigue continues for atleast 6 months then it is called as chronic fatigue or longer with other known medical conditions (whose manifestation includes fatigue) excluded by clinical diagnosis; and
  2. Concurrently have four or more of the following symptoms:
  • post-exertional malaise
  • impaired memory or concentration
  • unrefreshing sleep
  • muscle pain
  • multi joint pain without redness or swelling
  • tender cervical or axillary lymph node
  • sore throat
  • Head ache
  • Other words that a person might use to describe fatigue may include:
  • lethargic,
  • listless,
  • lack of energy,
  • tired,
  • worn out,
  • weary,
  • exhausted,
  • malaise, or
  • feeling run down.

Differential Diagnosis

Sleep disorders:

The fatigue can be caused by sleep disorders.  Obstructive sleep apnea, restless leg syndrome and insomnia might result is sleep disorders.

Medical problems:

Fatigue is a common symptom in several medical conditions, such as anemia, diabetes and underactive thyroid (hypothyroidism). Lab tests can check your blood for evidence of some of the top suspects.

Mental health issues:

 Fatigue is also a symptom of a variety of mental health problems, such as depression and anxiety. A counselor can help determine if one of these problems is causing your fatigue.

Diagnostic criteria

Guidelines proposed by the United States Institute of Medicine define the fatigue associated with chronic fatigue syndrome as being:

  • So severe that it interferes with the ability to engage in pre-illness activities
  • Of new or definite onset (not lifelong)
  • Not substantially alleviated by rest
  • Worsened by physical, mental or emotional exertion

To meet the Institute of Medicine's diagnostic criteria for chronic fatigue syndrome, a person would also need to experience at least one of these two symptoms:

  • Difficulties with memory, focus and concentration
  • Dizziness that worsens with moving from lying down or sitting to standing


Avoid strenuous exercises

Maintain healthy lifestyle

If pain is chronic seek medical help

Keep the mind calm and avoid stress